Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia

Abstract

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. > 2 prior treatments, with equally good effectivity in standard risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.

Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database

“…While clinical trials demonstrate impressive benefit of darabased therapies, possible discordance with real-world practice might exist, as many patients in the real world are known to be ineligible for clinical trials. 22,23 A few small real-world multicentre studies specifically focusing on dara have been published, confirming the promising activity noted in clinical trials [23][24][25][26][27] [28][29][30][31] There remains a paucity of studies evaluating the outcomes of dara-containing regimens in larger realworld cohorts. Our study aimed to evaluate the impact of these regimens and to benchmark outcomes that may identify gaps that can be targeted for future optimization.…”

“…Indeed, in similar populations, an ORR of 40%-50% could be achieved with a short median PFS of less than 6 months. Some realworld studies used dara in combination with IMiDs 23,25 (Szabo et al, 2021) and PIs 25 (Harvanová et al, 2021;Szabo et al, 2021), although they often included less heavily pretreated patients. As for our study, combinations with IMiDs induce a higher rate of response (80%), a higher quality of response and a longer median PFS with lower advantages for DaraVD.…”

“…(Atrash et al, 2021;Harvanová et al, 2021;Maouche et al, 2021;Szabo et al, 2021). Additionally, many of these studies focused on patients receiving dara monotherapy[24][25][26][27] (Atrash et al, 2021; Maouche et al, 2021; Szabo et al, 2021…”

The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab‐containing line of therapy

“…Until recently, only a few studies have reported on the real-world use of daratumumab, and these reports were based on small patient cohorts. [1][2][3][4] Monoclonal Antibodies in Multiple Myeloma:…”

Review of daratumumab efficacy in all monoclonal gammopathies and other diseases and our experience with daratumumab, lenalidomide and dexamethasone therapy in 74 patients

“…Závěry této velké analýzy České myelomové skupiny jsou podobné jako závěry výše uvedené studie. Přínos daratumumabu pro nemocné s extramedulárním šířením myelomových buněk je podstatně menší než u pacientů bez extramedulárního šíření(110,111).Podobné výsledky má i analýza Slovenské myelomové skupiny(112). Menší efektivitu léčby daratumumabem při extramedulárních ložiscích ve srovnání s pacienty bez těchto extramedulárních ložisek zaznamenali i další autoři(113,114).Mnohočetný myelom může vytvářet i leptomeningeální poškození.…”